Chronic alcohol ingestion is a major etiologic factor in the development of carcinoma of both oral and esophageal epithelium. Epidemiologic studies in humans and laboratory experiments have shown a close association between alcohol ingestion and the development of signs of zinc deficiency. In zinc-deficient humans, dysplastic lesions develop in esophageal epithelium, and many of these individuals later develop carcinoma. These facts suggest that the effect of alcohol on the esophagus may be mediated by zinc deficiency. Zinc deficiency in rats leads to changes in oral and esophageal epithelium resembling those in the esophagus of zinc-deficient humans. But there is no information on the effect of alcohol ingestion on oral epithelium. The aim of the study described in this application is, firstly, to ascertain whether alcohol ingestion causes changes in oral epithelium of rats fed a zinc-sufficient diet and, secondly, to see if alcohol ingestion intensifies the signs of zinc deficiency in oral and esophageal epithelium in rats on a low-zinc diet. One group of rats will drink a 10% ethyl alcohol solution in distilled water and the other group will drink only distilled water. One half of each group of rats will be fed a diet containing 40 ppm zinc; the second half will receive the same diet except for the zinc content, which will be 1.8 ppm. The experiments will last five weeks. The following studies will be carried out on buccal and esophageal epithelium: light microscope examination for qualitative and quantitative changes in morphology; assessment of rate of proliferation via mitotic index after colchicine administration; determination of zinc content by atomic absorption spectroscopy. Serum and kidney zinc levels will be assayed in all rats to assess the effects of alcohol on the general zinc status. If this pilot study shows that alcohol does cause dysplastic changes in rat oral epithelium, the basis will have been laid for future studies on the mechanisms involved.